1. MMP-25 Metalloprotease Regulates Innate Immune Response through NF-κB Signaling
- Author
-
Fernando G. Osorio, M. Soledad Fernández-García, Ana Gutiérrez-Fernández, Elena Bonzón-Kulichenko, Jesús Vázquez, Antonio Fueyo, Enrique Colado, Carlos López-Otín, Dido Carrero, Adolfo A. Ferrando, and Clara Soria-Valles
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Chemokine ,Matrix Metalloproteinases, Membrane-Associated ,Immunology ,chemical and pharmacologic phenomena ,GPI-Linked Proteins ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,Immune system ,Hypergammaglobulinemia ,Leukocytes ,Immunology and Allergy ,Animals ,Secretion ,Cells, Cultured ,Mice, Knockout ,Metalloproteinase ,Innate immune system ,biology ,NF-kappa B ,NFKB1 ,Immunity, Innate ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,biology.protein ,Cytokines ,Signal transduction ,Inflammation Mediators ,Protein Binding ,Signal Transduction - Abstract
Matrix metalloproteases (MMPs) regulate innate immunity acting over proinflammatory cytokines, chemokines, and other immune-related proteins. MMP-25 (membrane-type 6-MMP) is a membrane-bound enzyme predominantly expressed in leukocytes whose biological function has remained largely unknown. We have generated Mmp25-deficient mice to elucidate the in vivo function of this protease. These mutant mice are viable and fertile and do not show any spontaneous phenotype. However, Mmp25-null mice exhibit a defective innate immune response characterized by low sensitivity to bacterial LPS, hypergammaglobulinemia, and reduced secretion of proinflammatory molecules. Moreover, these immune defects can be tracked to a defective NF-κB activation observed in Mmp25-deficient leukocytes. Globally, our findings provide new mechanistic insights into innate immunity through the activity of MMP-25, suggesting that this proteinase could be a potential therapeutic target for immune-related diseases.
- Published
- 2016